Developmental Shift From Intrinsic Hyper‐ to Hypo‐Connectivity Occurring at Pre‐Adolescence in Autism Spectrum Disorder

Accumulating evidence suggests that hyper-connectivity is more characteristic of young children with autism spectrum disorder (ASD), while hypo-connectivity begins to emerge in adolescence and persists into adulthood. Despite increasing efforts being invested to explore the altered functional connectivity in ASD, the timing of the shift from intrinsic hyper-to hypo-connectivity of large-scale brain functional networks remains unclear. Here, we systematically depict the development of intrinsic functional connectivity in 800 participants from the Autism Brain Imaging Data Exchange. We first use independent component analyses to identify the large-scale brain functional networks. Then, we utilize the locally estimated scatterplot smoothing algorithm to fit the developmental trajectory of brain functional networks. Finally, we develop a "sliding threshold" method to detect the age stage at which the shift from hyper- to hypo-connectivity occurs in ASD. We identify six large-scale brain functional networks, including the default mode network (DMN), fronto-parietal network (FPN), salience network (SAN), auditory network (AN), somatomotor network (SMN), and visual network (VN). We find that primary networks (AN, SMN, and VN) undergo the shift from hyper- to hypo-connectivity earlier than high-order networks (DMN, FPN, and SAN) in ASD. At pre-adolescence, the SMN, AN, VN, DMN, SAN, and FPN undergo the shift from hyper- to hypo-connectivity in sequence in ASD. Our findings shed light on the age-related changes of intrinsic functional connectivity in ASD, highlighting the need for conceptualizing functional connectivity in ASD from a developmental perspective.